tbuckley/cabot-search huggingface dataset:
Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines
Authors: Paola Benaglio, Han Zhu, Mei-Lin Okino, Jian Yan, Ruth Elgamal, Naoki Nariai, Elisha Beebe, Katha Korgaonkar, Yunjiang Qiu, Margaret K.R. Donovan, Joshua Chiou, Gaowei Wang, Jacklyn Newsome, Jaspreet Kaur, Michael Miller, Sebastian Preissl, Sierra Corban, Anthony Aylward, Jussi Taipale, Bing Ren, Kelly A. Frazer, Maike Sander, Kyle J. Gaulton
Journal: Cell Genomics (2022)

We combined functional genomics and human genetics to investigate processes that affect type 1 diabetes (T1D) risk by mediating beta cell survival in response to proinflammatory cytokines. We mapped 38,931 cytokine-responsive candidate cis-regulatory elements (cCREs) in beta cells using ATAC-seq and snATAC-seq and linked them to target genes using co-accessibility and HiChIP. Using a genome-wide CRISPR screen in EndoC-βH1 cells, we identified 867 genes affecting cytokine-induced survival, and genes promoting survival and up-regulated in cytokines were enriched at T1D risk loci. Using SNP-SELEX, we identified 2,229 variants in cytokine-responsive cCREs altering transcription factor (TF) binding, and variants altering binding of TFs regulating stress, inflammation, and apoptosis were enriched for T1D risk. At the 16p13 locus, a fine-mapped T1D variant altering TF binding in a cytokine-induced cCRE interacted with SOCS1, which promoted survival in cytokine exposure. Our findings reveal processes and genes acting in beta cells during inflammation that modulate T1D risk.
High Burden of Undiagnosed Hepatitis B and Liver Disease in an Urban Emergency Department—Baltimore, 2020
Authors: Richard Wang, Richard E. Rothman, Amir M. Mohareb, Oliver Laeyendecker, Gavin A. Cloherty, Thomas C. Quinn, Yu-Hsiang Hsieh, Mark Anderson, Sunil S. Solomon, Reinaldo E. Fernandez, Gaby Dashler, Radhika Mehta, Michael Stec, Thomas Kickler, Gabor D. Kelen, Shruti H. Mehta, Evan J. Beck, Sharada Saraf, Owen R. Baker, Isabel V. Lake, Erin P. Ricketts, Danna Anderson, Jennifer Hurley
Journal: Clinical Gastroenterology and Hepatology (2022)
AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models
Authors: Maria Clara Selles, Juliana T.S. Fortuna, Magali C. Cercato, Luis Eduardo Santos, Luciana Domett, Andre L.B. Bitencourt, Mariane Favero Carraro, Amanda S. Souza, Helena Janickova, Caroline Vieira Azevedo, Henrique Correia Campos, Jorge M. de Souza, Soniza Alves-Leon, Vania F. Prado, Marco A.M. Prado, Alberto L. Epstein, Anna Salvetti, Beatriz Monteiro Longo, Ottavio Arancio, William L. Klein, Adriano Sebollela, Fernanda G. De Felice, Diana A. Jerusalinsky, Sergio T. Ferreira
Journal: Molecular Therapy (2022)

The accumulation of soluble oligomers of the amyloid-β peptide (AβOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AβOs and shows minimal reactivity to Aβ monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AβO binding to neurons and AβO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AβO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.
Author Correction: Synergistic checkpoint-blockade and radiotherapy–radiodynamic therapy via an immunomodulatory nanoscale metal–organic framework
Authors: Kaiyuan Ni, Ziwan Xu, August Culbert, Taokun Luo, Nining Guo, Kaiting Yang, Erik Pearson, Ben Preusser, Tong Wu, Patrick La Riviere, Ralph R. Weichselbaum, Michael T. Spiotto, Wenbin Lin
Journal: Nature Biomedical Engineering (2022)
Correction: Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing
Authors: Nina Kessler, Susanne F. Viehmann, Calvin Krollmann, Karola Mai, Katharina M. Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M.C. Böhner, Dennis Huugen, Carina C. de Oliveira Mann, Simon Otten, Stefanie A.I. Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E. Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A. Lyons, Peter Boor, Angela Rösen-Wolff, Lino L. Teichmann, Peter Heeringa, Christian Kurts, Natalio Garbi
Journal: The Journal of Experimental Medicine (2022)
Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFNγ-cGAS-STING axis
Authors: Xu Wang, Chao Yang, Xuejie Wang, Jinmin Miao, Weitao Chen, Yiren Zhou, Ying Xu, Yongyan An, Aifang Cheng, Wenkang Ye, Mengxian Chen, Dong Song, Xue Yuan, Jiguang Wang, Peiyuan Qian, Angela Ruohao Wu, Zhong-Yin Zhang, Kai Liu
Journal: Neuron (2022)

The coordination mechanism of neural innate immune responses for axon regeneration is not well understood. Here, we showed that neuronal deletion of protein tyrosine phosphatase non-receptor type 2 sustains the IFNγ-STAT1 activity in retinal ganglion cells (RGCs) to promote axon regeneration after injury, independent of mTOR or STAT3. DNA-damage-induced cGAMP synthase (cGAS)-stimulator of interferon genes (STINGs) activation is the functional downstream signaling. Directly activating neuronal STING by cGAMP promotes axon regeneration. In contrast to the central axons, IFNγ is locally translated in the injured peripheral axons and upregulates cGAS expression in Schwann cells and infiltrating blood cells to produce cGAMP, which promotes spontaneous axon regeneration as an immunotransmitter. Our study demonstrates that injured peripheral nervous system (PNS) axons can direct the environmental innate immune response for self-repair and that the neural antiviral mechanism can be harnessed to promote axon regeneration in the central nervous system (CNS).
AMA members retirement plan
Journal: JAMA (1968)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Genetic and epigenetic defects of the RNA modification machinery in cancer
Authors: Ines Orsolic, Arnaud Carrier, Manel Esteller
Journal: Trends in Genetics (2022)

Cancer was initially considered to be an exclusively genetic disease, but an interplay of dysregulated genetic and epigenetic mechanisms is now known to contribute to the cancer phenotype. More recently, chemical modifications of RNA molecules - the so-called epitranscriptome - have been found to regulate various aspects of RNA function and homeostasis. Specific enzymes, known as RNA-modifying proteins (RMPs), are responsible for depositing, removing, and reading chemical modifications in RNA. Intensive investigations in the epitranscriptomic field in recent years, in conjunction with great technological advances, have revealed the critical role of RNA modifications in regulating numerous cellular pathways. Furthermore, growing evidence has revealed that RNA modification machinery is often altered in human cancers, highlighting the enormous potential of RMPs as pharmacological targets or diagnostic markers.
Premature aging as an accumulation of deficits in young adult survivors of pediatric cancer
Authors: AnnaLynn M Williams, Jeanne Mandelblatt, Mingjuan Wang, Gregory T Armstrong, Nickhill Bhakta, Tara M Brinkman, Wassim Chemaitilly, Matthew J Ehrhardt, Daniel A Mulrooney, Brent J Small, Zhaoming Wang, Deokumar Srivastava, Leslie L Robison, Melissa M Hudson, Kirsten K Ness, Kevin R Krull
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared with community controls and examine associations with host and treatment factors, neurocognition, and mortality. Methods Pediatric cancer survivors (n = 4000, median age = 28.6, interquartile range [IQR] = 23-35 years; 20 years postdiagnosis: IQR = 15-27), and community participants without a history of cancer serving as controls (n = 638, median age = 32, IQR = 25-40 years) completed clinical assessments and questionnaires and were followed for mortality through April 30, 2020 (mean [SD] follow-up = 7.0 [3.4] years). A deficit accumulation index (DAI) score was calculated from 44 aging-related items including self-reported daily function, psychosocial symptoms, and health conditions. Items were weighted from 0 (absent) to 1 (present and/or most severe), summed and divided by the total yielding a ratio (higher = more deficits). Scores less than 0.20 are robust, and 0.06 is a clinically meaningful difference. Linear regression compared the DAI in survivors and controls with an age*survivor or control interaction. Logistic regression and Cox-proportional hazards estimated the risk of neurocognitive impairment and death. Models were minimally adjusted for age, sex, and race and ethnicity. Results The adjusted mean DAI among survivors at age 30 years was 0.16 corresponding to age 63 years in controls (33 years premature aging; β = 0.07, 95% confidence interval [CI] = 0.06 to 0.08; P &amp;lt; .001). Cranial and abdominal radiation, alkylators, platinum, and neurosurgery were associated with worse DAI (P ≤ .001). Higher scores were associated with increased risk of neurocognitive impairment in all domains (P &amp;lt; .001) and increased risk of death (DAI = 0.20-0.35, hazard ratio = 2.80, 95% CI = 1.97 to 3.98; DAI ≥ 0.35, hazard ratio = 5.08, 95% CI = 3.52 to 7.34). Conclusion Pediatric cancer survivors experience clinically significant premature aging. The DAI may be used to identify survivors at greatest risk of poor health outcomes.
More than half of patients with a rheumatic disease or immunologic condition undergoing methotrexate treatment reside in states in which the overturning of Roe v. Wade can jeopardize access to medications with abortifacient potential
Authors: Kathryn Starzyk, Veena Hoffman, Zhaohui Su, Roger Meng, Mudit Bhartia, Gary Curhan, Kazuki Yoshida, Jessica K. Paulus
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Peroral direct cholangioscopy using balloon endoscopy for massive bile duct stones after Roux-en-Y hepaticojejunostomy
Authors: Masatoshi Murakami, Nao Fujimori, Toyoma Kaku
Journal: Endoscopy (2022)

A 63-year-old man with acute cholangitis was admitted to our hospital. He had undergone pancreaticoduodenectomy with Roux-en-Y hepaticojejunostomy for a duodenal ulcer 13 years previously. The patient was referred to our hospital for stone extraction after undergoing endoscopic retrograde cholangiopancreatography with plastic biliary stent placement.
Prognostic significance of radiological pleuroparenchymal fibroelastosis in<i>Mycobacterium avium</i>complex lung disease: a multicentre retrospective cohort study
Authors: Yuya Aono, Hironao Hozumi, Masato Kono, Dai Hashimoto, Hidenori Nakamura, Koshi Yokomura, Shiro Imokawa, Masahiro Shirai, Daisuke Akahori, Yusuke Inoue, Kazutaka Mori, Masato Karayama, Yuzo Suzuki, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Takafumi Suda
Journal: Thorax (2022)

Background Mycobacterium avium complex (MAC) causes chronic respiratory infectious diseases with diverse clinical features and prognoses. Pleuroparenchymal fibroelastosis (PPFE) is a rare disease characterised by pleural fibrosis with subjacent intra-alveolar fibrosis and alveolar septal elastosis, with unique chest high-resolution CT (HRCT) features (radiological PPFE). An association between recurrent respiratory infections and PPFE formation has been hypothesised; however, the clinical significance of PPFE in MAC lung disease remains unclear. Methods This retrospective, multicentre study investigated the prevalence of radiological PPFE in patients with MAC lung disease and its association with clinical features and outcomes. Radiological PPFE was diagnosed on the basis of HRCT findings. Prognostic factors were identified using Cox proportional hazards and Fine-Gray models. Results Of 850 consecutive patients with definite MAC lung disease, 101 (11.9%) exhibited radiological PPFE. Patients with radiological PPFE had unique characteristics, such as lower body mass index, lower survival rate (5-year cumulative survival rate, 63.1% vs 91.7%; p&lt;0.001) and a higher incidence of respiratory-related death (5-year cumulative incidence, 31.1% vs 3.6%; p&lt;0.001), than those without radiological PPFE. In the multivariable analysis, the presence of radiological PPFE was independently associated with all-cause mortality (adjusted HR, 4.78; 95% CI, 2.87 to 7.95; p&lt;0.001) and respiratory-related death (adjusted HR, 3.88; 95% CI, 2.14 to 7.01; p&lt;0.001). Interpretation This large-scale study demonstrated that in patients with MAC lung disease, radiological PPFE was common, a phenotype associated with unique clinical features and poor prognosis, particularly respiratory-related death. The specific management of this subgroup should be established.
Closure of a gastric endoscopic resection defect with a novel closure device
Authors: Natalie Wilson, Long B. Le, Mohamed Abdallah, Mohammad Bilal
Journal: Endoscopy (2022)

Closure of mucosal defects after endoscopic mucosal resection or endoscopic submucosal dissection (ESD) has been shown to reduce the risk of delayed bleeding and perforation [1] [2] [3] [4]. Defect closure can be achieved using over-the-scope (OTS) clips, through-the-scope (TTS) clips, or endoscopic suturing [4].
Bile duct radiofrequency ablation for a residual adenoma after endoscopic papillectomy
Authors: Kotaro Takeshita, Susumu Hijioka, Kosuke Maehara, Yuta Maruki, Yoshikuni Nagashio, Takuji Okusaka, Yutaka Saito
Journal: Endoscopy (2022)

For residual or local recurrence of duodenal ampullary adenoma after endoscopic papillectomy, argon plasma coagulation (APC) has been reported to be useful; however, APC may be insufficient because deep or circumferential ablation in the distal bile duct is difficult to perform [1]. Recently, the usefulness of bile duct radiofrequency ablation (RFA) for residual adenomas has been reported, but the number of cases is still relatively small [2] [3]. We report a case in which bile duct RFA was performed on a residual adenoma after endoscopic papillectomy.
Two-step pancreatic duct stenting with endoscopic ultrasonography and balloon-assisted enteroscopy for pancreaticojejunal anastomotic stricture
Authors: Kosuke Nagai, Masaki Kuwatani, Yunosuke Takishin, Ryutaro Furukawa, Hajime Hirata, Kazumichi Kawakubo, Naoya Sakamoto
Journal: Endoscopy (2022)

A 75-year-old woman was referred to our hospital for treatment of pancreaticojejunal anastomotic stricture (PJS) after pancreaticoduodenectomy for pancreatic head cancer. Although balloon-assisted enteroscopy was performed, the PJS could not be cannulated by a catheter owing to occlusion. Endoscopic ultrasonography (EUS)-guided pancreatic drainage was performed via the stomach at the main pancreatic duct (MPD) adjacent to the PJS using a 7-Fr plastic stent because puncture of the distal MPD was difficult ([Fig. 1], [Fig. 2], [Video 1]). Three months later, computed tomography (CT) revealed dilation of the MPD due to the insufficient length of the stent passed through the MPD ([Fig. 3]). Therefore. we planned to place another stent into the MPD from the jejunal side using balloon-assisted enteroscopy.
Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase <scp>II</scp>, Randomized, <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp> Trial
Authors: Eric Morand, Marilyn Pike, Joan T. Merrill, Ronald van Vollenhoven, Victoria P. Werth, Coburn Hobar, Nikolay Delev, Vaishali Shah, Brian Sharkey, Thomas Wegman, Ian Catlett, Subhashis Banerjee, Shalabh Singhal
Journal: Arthritis & Rheumatology (2022)

To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE).
High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer
Authors: Stefan Salcher, Gregor Sturm, Lena Horvath, Gerold Untergasser, Christiane Kuempers, Georgios Fotakis, Elisa Panizzolo, Agnieszka Martowicz, Manuel Trebo, Georg Pall, Gabriele Gamerith, Martina Sykora, Florian Augustin, Katja Schmitz, Francesca Finotello, Dietmar Rieder, Sven Perner, Sieghart Sopper, Dominik Wolf, Andreas Pircher, Zlatko Trajanoski
Journal: Cancer Cell (2022)

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune cell infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how immune cell phenotypes vary across different patient subgroups is lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution by integrating 1,283,972 single cells from 556 samples and 318 patients across 29 datasets, including our dataset capturing cells with low mRNA content. We stratify patients into immune-deserted, B cell, T cell, and myeloid cell subtypes. Using bulk samples with genomic and clinical information, we identify cellular components associated with tumor histology and genotypes. We then focus on the analysis of tissue-resident neutrophils (TRNs) and uncover distinct subpopulations that acquire new functional properties in the tissue microenvironment, providing evidence for the plasticity of TRNs. Finally, we show that a TRN-derived gene signature is associated with anti-programmed cell death ligand 1 (PD-L1) treatment failure.
A novel triple stenting in the treatment of post-choledochojejunostomy reflux cholangitis
Authors: Kosuke Maehara, Susumu Hijioka, Yuki Kawasaki, Kiichi Tamada, Takuji Okusaka, Yutaka Saito
Journal: Endoscopy (2022)

Reflux cholangitis is a known complication following choledochojejunostomy [1]. It is believed that this disease can develop owing to afferent loop syndrome without choledochojejuno-anastomotic stenosis [2] [3]. Treating the condition by placing the Duckbill-type antireflux self-expandable metal stent (D-ARMS; Kawasumi Laboratories, Tokyo, Japan) at the anastomosis has been reported previously [4]. However, the stenting of three D-ARMSs to each bile duct has never been reported. We report the case of a patient with a large anastomosis and post-choledochojejunostomy reflex cholangitis (PCRC), treated using placement of three D-ARMSs ([Video 1]).
Troubleshooting with a drill dilator for the stent-in-stent technique in malignant hilar biliary obstruction
Authors: Manabu Yamada, Takeshi Okamoto, Naoki Sasahira
Journal: Endoscopy (2022)

The stent-in-stent (SIS) technique is often used for endoscopic treatment of malignant hilar biliary obstruction and has a high success rate [1]. While the technique allows for placement of three or more stents, passing delivery systems through the mesh of a previously placed self-expandable metal stent (SEMS) can be difficult [1] [2]. We report successful troubleshooting with Tornus ES, a drill dilator, during three-way SEMS placement ([Fig. 1]).
Inherited Cancer Susceptibility Gene Sequence Variations Among Patients With Appendix Cancer
Authors: Andreana N. Holowatyj, Mary K. Washington, Sean V. Tavtigian, Cathy Eng, Carolyn Horton
Journal: JAMA Oncology (2022)

Germline sequence variations in APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53 genes are associated with susceptibility to gastrointestinal cancers. As a rare cancer, the evaluation of appendiceal cancer (AC) predisposition has been limited.